Adaptive trial in severe pneumonia (REMAP-CAP)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 6800

Inclusion Criteria

General REMAP-CAP Inclusion Criteria:

1. Adult patient admitted to an ICU for acute severe CAP within 48 hours of hospital admission with
a. symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain) AND
b. Radiological evidence of new onset infiltrate of infective origin (in patients with pre-existing radiological changes, evidence of new infiltrate).

2. Up to 48 hours after ICU admission, receiving organ support with one or more of:
a. Non-invasive or invasive ventilatory support;
b. Receiving infusion of vasopressor or inotropes or both.

DOMAIN LEVEL: Domain specific inclusion criteria
Macrolide Domain: Patients are eligible for this domain only if they have been allocated a beta-lactam plus macrolide intervention within the Antibiotic Domain.
Influenza Antiviral Domain: Influenza infection is confirmed by microbiological testing.
Anticoagulation Domain: COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing. Microbiological testing for SARS-CoV-2 of upper or lower respiratory tract secretions or both has occurred or is intended to occur.
Antiplatelet Domain: COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing. Microbiological testing for SARS-CoV-2 of upper or lower respiratory tract secretions or both has occurred or is intended to occur.
Mechanical Ventilation Domain: Receiving invasive mechanical ventilation. The most recent PaO2:FiO2 ratio obtained within the preceding 6 hours is less than 200 mmHg. Treating clinician expects the patient to still require invasive mechanical ventilation tomorrow. Treating clinician regards Protocolized Mechanical Ventilation Strategy or their preferred mode as (equally) appropriate for this patient.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2000

Exclusion Criteria

General platform exclusion criteria (Core Protocol):
1. Healthcare-associated pneumonia:
a) Prior to this, is known to have has been an inpatient in any healthcare facility within the last 30 days
b) Resident of a nursing home or long-term care facility
2. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
3. Previous participation in this REMAP within the last 90 days

Exclusion criteria for the pandemic aspects of REMAP-CAP:
1. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
2. Patient is expected to be discharged from hospital today or tomorrow
3. More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection
4. Previous participation in this REMAP within the last 90 days.

There are domain-specific exclusion criteria in the Antibiotic, macrolide
duration, Influenza Antiviral Domain, Anticoagulation Domain, Mechanical Ventilation Domain, Antiplatelet Domain and Corticosteroid domain. These have not changed compared to previous submissions. Due to maximum number of characters, only the domain-specific and
interaction-specific exclusions for the adjusted Influenza Antiviral domain and new Immune Modulation Influenza domain are mentioned below.

Influenza Antiviral Domain:
Patients will be excluded from this domain if they have any of the following:
• If in the Moderate State, more than 96 hours has elapsed since hospital admission
• If in the Severe State, more than 48 hours has elapsed since ICU admission, unless the patient has already been assigned a treatment in another domain in the Moderate State, in which case exclusion will occur if more than 48 hours has elapsed since commencement of sustained organ failure support in an ICU
• Patient has already received two or more doses of oseltamivir or other neuraminidase inhibitors
• Patient has already received one or more doses of baloxavir
• Patient is already receiving, or a clinical decision has been made to commence, an antiviral active against influenza other than oseltamivir or baloxavir or both.
• The treating clinician believes that participation in the domain would not be in the best interests of the patient

Immune Modulation Influenza domain:
Patients will be excluded from this domain if they have any of the following:
• SARS-CoV-2 infection has been confirmed by microbiological testing
• Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization
• A neutrophil count <1.0 x 109 / L
• Confirmed or strongly-suspected active mycobacterial infection or invasive fungal infection
• Patient has already received any dose of one or more of any form of tocilizumab or another IL-6 receptor antagonist (e.g. sarilumab), baricitinib or another JAK inhibitor (e.g. tofacitinib, ruxolitinib or upadacitinib) during this hospitalization or is on long-term therapy with any of these agents prior to this hospital admission.
• The treating clinician believes that participation in the domain would not be in the best interests of the patient

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials

Adaptive trial in severe pneumonia Coronavirus COVID-19 (REMAP-CAP-COVID-19)

Phase 1

niversity Medical Center Utrecht

Updated 4/6/2020